PT  - JOURNAL ARTICLE
AU  - Andrew D.  Foers
AU  - Alexandra L.  Garnham
AU  - Gordon K.  Smyth
AU  - Susanna M.  Proudman
AU  - Lesley Cheng
AU  - Andrew F.  Hill
AU  - Ken C.  Pang
AU  - Ian P.  Wicks
TI  - Circulating Small Noncoding RNA Biomarkers of Response to Triple Disease-modifying Antirheumatic Drug Therapy in White Women With Early Rheumatoid Arthritis
AID  - 10.3899/jrheum.191012
DP  - 2020 Jun 15
TA  - The Journal of Rheumatology
PG  - jrheum.191012
4099  - http://www.jrheum.org/content/early/2020/10/13/jrheum.191012.short
4100  - http://www.jrheum.org/content/early/2020/10/13/jrheum.191012.full
AB  - Objective To identify small noncoding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA). Methods Early RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as European League Against Rheumatism responders or nonresponders. RNA was isolated from 42 archived serum samples, collected prior to commencement of triple DMARD therapy. Small RNA sequencing was performed and the reads mapped to annotations in a database of human sncRNA. Differential expression analysis was performed, comparing responders (n = 24) and nonresponders (n = 18). Results Pretreatment levels of 4 sncRNA were significantly increased in nonresponders: chr1.tRNA131‑GlyCCC (4.1-fold, adjusted P = 0.01), chr2.tRNA13-AlaCGC (2.2-fold, adjusted P = 0.02), U2-L166 (6.6-fold, adjusted P = 0.02), and piR-35982 (2.4-fold, adjusted P = 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adjusted P = 0.01). Reads for chr1.tRNA131‑GlyCCC and chr2.tRNA13-AlaCGC mapped to the 5ʹ end of each tRNA gene and were truncated at the anticodon loop, consistent with these sncRNA having roles as 5ʹ translation interfering tRNA halves (tiRNA). Conclusion Pretreatment levels of specific serum sncRNA might facilitate identification of patients more likely to respond to triple DMARD therapy.